MOLECULAR-ORIGIN OF CONTINUOUS DARK NOISE IN ROD PHOTORECEPTORS

Noise in the rod photoreceptors limits the ability of the dark-adapted visual system to detect dim lights. We investigated the molecular mec hanism of the continuous component of the electrical dark noise in toa d rods. Membrane current was recorded from intact, isolated rods or tr uncated, internally dialyzed rod outer segments. The continuous noise was separated from noise due to thermal activation of rhodopsin and to transitions in the cGMP-activated channels. Selectively disabling dif ferent elements of the phototransduction cascade allowed examination o f their contributions to the continuous noise. These experiments indic ate that the noise is generated by spontaneous activation of cGMP phos phodiesterase (PDE) through a process that does not involve transducin . The addition of recombinant gamma, the inhibitory subunit of PDE, di d not suppress the noise, indicating that endogenous gamma does not co mpletely dissociate from the catalytic subunit of PDE during spontaneo us activation. Quantitative analysis of the noise provided estimates o f the rate constants for spontaneous PDE activation and deactivation a nd the catalytic activity of a single PDE molecule in situ.